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Infusions of the short-chain fatty acid (SCFA) acetate in the distal colon improved metabolic parameters in men. Here, we hypothesized that combining rapidly and slowly fermentable fibers will enhance distal colonic acetate production and improve metabolic health. In vitro cultivation studies in a validated model of the colon were used to identify fiber mixtures that yielded high distal colonic acetate production. Subsequently, in two randomized crossover studies, lean and prediabetic overweight/obese men were included. In one study, participants received supplements of either long-chain inulin+resistant starch (INU+RS), INU or maltodextrin (PLA) the day prior to a clinical investigation day (CID). The second trial studied beta glucan+RS (BG+RS) versus BG and PLA. During each CID, breath hydrogen, indirect calorimetry, plasma metabolites/hormones were assessed during fasting and postprandial conditions. Additionally, fecal microbiota composition and SCFA were determined. In prediabetic men, INU+RS increased plasma acetate compared to INU or PLA (P < .05), but did not affect metabolic parameters. In lean men, INU+RS increased breath hydrogen and fasting plasma butyrate, which was accompanied by increased energy expenditure, carbohydrate oxidation and PYY and decreased postprandial glucose concentrations (all P < .05) compared to PLA. BG+RS increased plasma butyrate compared to PLA (P < .05) in prediabetic individuals, but did not affect other fermentation/metabolic markers in both phenotypes. Fiber-induced shifts in fecal microbiota were individual-specific and more pronounced with INU+RS versus BG+RS. Administration of INU+RS (not BG+RS) the day prior to investigation improved metabolic parameters in lean but not in prediabetic individuals, demonstrating that effects were phenotype- and fiber-specific. Further research should study whether longer-term supplementation periods are required to elicit beneficial metabolic health in prediabetic individuals. Trial registration numbers: Clinical trial No. NCT03711383 (Inulin study) and Clinical trial No. NCT03714646 (Beta glucan study).

Evidence is accumulating that the gut microbiome is involved in the aetiology of obesity and obesity-related complications such as nonalcoholic fatty liver disease (NAFLD), insulin resistance and type 2 diabetes mellitus (T2DM). The gut microbiota is able to ferment indigestible carbohydrates (for example, dietary fibre), thereby yielding important metabolites such as short-chain fatty acids and succinate. Numerous animal studies and a handful of human studies suggest a beneficial role of these metabolites in the prevention and treatment of obesity and its comorbidities. Interestingly, the more distal colonic microbiota primarily ferments peptides and proteins, as availability of fermentable fibre, the major energy source for the microbiota, is limited here. This proteolytic fermentation yields mainly harmful products such as ammonia, phenols and branched-chain fatty acids, which might be detrimental for host gut and metabolic health. Therefore, a switch from proteolytic to saccharolytic fermentation could be of major interest for the prevention and/or treatment of metabolic diseases. This Review focuses on the role of products derived from microbial carbohydrate and protein fermentation in relation to obesity and obesity-associated insulin resistance, T2DM and NAFLD, and discusses the mechanisms involved.

Our recent in vivo human studies showed that colonic administration of sodium acetate (SA) resulted in increased circulating acetate levels, which was accompanied by increments in whole-body fat oxidation in overweight-obese men. Since skeletal muscle has a major role in whole-body fat oxidation, we aimed to investigate effects of SA on fat oxidation and underlying mechanisms in human primary skeletal muscle cells (HSkMC). We investigated the dose (0–5 mmol/L) and time (1, 4, 20, and 24 h) effect of SA on complete and incomplete endogenous and exogenous oxidation of 14C-labeled palmitate in HSkMC derived from a lean insulin sensitive male donor. Both physiological (0.1 and 0.25 mmol/L) and supraphysiological (0.5, 1 and 5 mmol/L) concentrations of SA neither increased endogenous nor exogenous fat oxidation over time in HSkMC. In addition, no effect of SA was observed on Thr172-AMPKα phosphorylation. In conclusion, our previously observed in vivo effects of SA on whole-body fat oxidation in men may not be explained via direct effects on HSkMC fat oxidation. Nevertheless, SA-mediated effects on whole-body fat oxidation may be triggered by other mechanisms including gut-derived hormones or may occur in other metabolically active tissues.

Growing evidence indicates an important link between gut microbiota, obesity, and metabolic syndrome. Alterations in exocrine pancreatic function are also widely present in patients with diabetes and obesity. To examine this interaction, C57BL/6J mice were fed either a chow diet, high-fat diet (HFD) or HFD plus oral vancomycin or metronidazole to modify the gut microbiome. HFD alone leads to a 40% increase in pancreas weight, decreased glucagon-like peptide-1 and peptide YY levels, and increased glucose-dependent insulinotropic peptide in the plasma. Quantitative proteomics identified 138 host proteins in fecal samples of these mice, of which 32 were significantly changed by HFD. The most significant of these were the pancreatic enzymes. These changes in amylase and elastase were reversed by antibiotic treatment. These alterations could be reproduced by transferring gut microbiota from donor C57BL/6J mice to germ-free. By contrast, antibiotics had no effect on pancreatic size or exocrine function in C57BL/6J mice fed a chow diet. Further, one week vancomycin administration significantly increased amylase and elastase levels in obese prediabetic men. Thus, the alterations in gut microbiota in obesity can alter pancreatic growth, exocrine function and gut endocrine function, and may contribute to the alterations observed in patients with obesity and diabetes.

The gut microbiota may affect host metabolic health through microbial metabolites. The balance between the production of microbial metabolites by saccharolytic and proteolytic fermentation may be an important determinant of metabolic health. Amongst the best-studied saccharolytic microbial metabolites are the short-chain fatty acids acetate, propionate and butyrate. However, human data on the role of other microbial fermentation by-products in metabolic health are greatly lacking. Therefore, we compared in a cross-sectional study the faecal microbial metabolites (caproate, lactate, valerate, succinate, and the branched-chain fatty acids (BCFA) (isobutyrate, isovalerate)) between insulin sensitive (homeostatic model assessment of insulin resistance (HOMA-IR), HOMA-IR1.85, IR) individuals. Additionally, we assessed the relationships between faecal metabolites and markers of metabolic health including fasting glucose, insulin, free fatty acids, insulin resistance (HOMA-IR) and fasting substrate oxidation in 86 individuals with a wide range of body mass index. Faecal metabolite concentrations did not significantly differ between IS and IR. Furthermore, there were no associations between microbial metabolites and metabolic health markers, except for a slight positive association of isovalerate with carbohydrate oxidation (E%, std β 0.194, P=0.011) and fat oxidation (E%, std β -0.075, P=0.047), also after adjustment for age, sex and BMI. In summary, faecal caproate, lactate, valerate, succinate, and BCFA (isobutyrate, isovalerate) were not different between IR and IS individuals, nor was there any association between these faecal metabolites and parameters of metabolic health. Further human intervention studies are warranted to investigate the role of these microbially-derived fermentation products and their kinetics in metabolic health and insulin sensitivity.

Accumulating evidence indicates that the gut microbiome is an important regulator of body weight, glucose and lipid metabolism, and inflammatory processes, and may thereby play a key role in the aetiology of obesity, insulin resistance and type 2 diabetes. Interindividual responsiveness to specific dietary interventions may be partially determined by differences in baseline gut microbiota composition and functionality between individuals with distinct metabolic phenotypes. However, the relationship between an individual’s diet, gut microbiome and host metabolic phenotype is multidirectional and complex, yielding a challenge for practical implementation of targeted dietary guidelines. In this review, we discuss the latest research describing interactions between dietary composition, the gut microbiome and host metabolism. Furthermore, we describe how this knowledge can be integrated to develop precision-based nutritional strategies to improve bodyweight control and metabolic health in humans. Specifically, we will address that (1) insight in the role of the baseline gut microbial and metabolic phenotype in dietary intervention response may provide leads for precision-based nutritional strategies; that (2) the balance between carbohydrate and protein fermentation by the gut microbiota, as well as the site of fermentation in the colon, seems important determinants of host metabolism; and that (3) ‘big data’, including multiple omics and advanced modelling, are of undeniable importance in predicting (non-)response to dietary interventions. Clearly, detailed metabolic and microbial phenotyping in humans is necessary to better understand the link between diet, the gut microbiome and host metabolism, which is required to develop targeted dietary strategies and guidelines for different subgroups of the population.

In 2019, we published a Review on the relevance of gut microbial metabolites in obesity, non-alcoholic fatty liver disease and type 2 diabetes mellitus. Here, we highlight the importance of the balance between colonic proteolytic and saccharolytic metabolite production for metabolic health and the need to focus on more subgroup-based or personalized nutritional approaches.

The following authors were omitted from the original version of this Data Descriptor: Markus Reichstein and Nicolas Vuichard. Both contributed to the code development and N. Vuichard contributed to the processing of the ERA-Interim data downscaling. Furthermore, the contribution of the co-author Frank Tiedemann was re-evaluated relative to the colleague Corinna Rebmann, both working at the same sites, and based on this re-evaluation a substitution in the co-author list is implemented (with Rebmann replacing Tiedemann). Finally, two affiliations were listed incorrectly and are corrected here (entries 190 and 193). The author list and affiliations have been amended to address these omissions in both the HTML and PDF versions. © 2021, This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.

Purpose of review To highlight recent research findings on effects of the short-chain fatty acid acetate in the control of body weight, insulin sensitivity, and glucose homeostasis. For this purpose, relevant animal and human in-vivo studies were reviewed and putative mechanisms and pathways were discussed. Recent findings Animal and human in-vivo studies provide strong indications for a beneficial role of orally ingested or colonically derived acetate, in the energy and substrate metabolism, thereby preventing or reversing the obese insulin-resistant phenotype. However, data from rodents are conflicting and indicate that an increased acetate turnover promotes body weight gain and insulin resistance. A reason for these controversies may be related to the mode and site of acetate administration, as well as to the species and the metabolic phenotype of animals used. Summary Overall, animal and human data suggest a direct regulatory role of acetate in several pathways involved in energy expenditure and fat utilization. In addition, acetate stimulates the release of gut-derived satiety-stimulating hormones and might regulate the inflammatory state. However, human intervention studies are required to evaluate the recent 'acetate discrepancies' and to confirm whether an increase in the acetate availability is a promising approach for the prevention and management of obesity and associated impairments in glucose and insulin metabolism.

Acute intake of the wheat bran extract Arabinoxylan-Oligosaccharide (AXOS) modulates the gut microbiota, improves stool characteristics and postprandial glycemia in healthy humans. Yet, little is known on how long-term AXOS intake influences gastrointestinal (GI) functioning, gut microbiota, and metabolic health. In this randomized, placebo-controlled, double-blind study, we evaluated the effects of AXOS intake on GI function and metabolic health in adults with slow GI transit without constipation. Forty-eight normoglycemic adults were included with whole-gut transit time (WGTT) of >35 h receiving either 15 g/day AXOS or placebo (maltodextrin) for 12-wks. The primary outcome was WGTT, and secondary outcomes included stool parameters, gut permeability, short-chain fatty acids (SCFA), microbiota composition, energy expenditure, substrate oxidation, glucose, insulin, lipids, gut hormones, and adipose tissue (AT) function. WGTT was unchanged, but stool consistency softened after AXOS. 12-wks of AXOS intake significantly changed the microbiota by increasing Bifidobacterium and decreasing microbial alpha-diversity. With a good classification accuracy, overall microbiota composition classified responders with decreased WGTT after AXOS. The incretin hormone Glucagon-like protein 1 was reduced after AXOS compared to placebo. Energy expenditure, plasma metabolites, AT parameters, SCFA, and gut permeability were unchanged. In conclusion, intake of wheat bran extract increases fecal Bifidobacterium and softens stool consistency without major effects on energy metabolism in healthy humans with a slow GI transit. We show that overall gut microbiota classified responders with decreased WGTT after AXOS highlighting that GI transit and change thereof were associated with gut microbiota independent of Bifidobacterium. NCT02491125

The FLUXNET2015 dataset provides ecosystem-scale data on CO2, water, and energy exchange between the biosphere and the atmosphere, and other meteorological and biological measurements, from 212 sites around the globe (over 1500 site-years, up to and including year 2014). These sites, independently managed and operated, voluntarily contributed their data to create global datasets. Data were quality controlled and processed using uniform methods, to improve consistency and intercomparability across sites. The dataset is already being used in a number of applications, including ecophysiology studies, remote sensing studies, and development of ecosystem and Earth system models. FLUXNET2015 includes derived-data products, such as gap-flled time series, ecosystem respiration and photosynthetic uptake estimates, estimation of uncertainties, and metadata about the measurements, presented for the frst time in this paper. In addition, 206 of these sites are for the frst time distributed under a Creative Commons (CC-BY 4.0) license. This paper details this enhanced dataset and the processing methods, now made available as open-source codes, making the dataset more accessible, transparent, and reproducible., European Union (EU), United States Department of Energy (DOE)

Microbially-produced acetate has been reported to beneficially affect metabolic health through effects on satiety, energy expenditure, insulin sensitivity, and substrate utilization. Here, we investigate the association between sex-specific concentrations of acetate and insulin sensitivity/resistance indices (Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), circulating insulin and Matsuda Index) in the Diet, Obesity and Genes (DiOGenes) Dietary study at baseline and after a low-calorie diet (LCD, 800 kcal/d). In this analysis, 692 subjects (Body Mass Index &gt, 27 kg/m2) were included, who underwent an LCD for 8 weeks. Linear mixed models were performed, which were adjusted for mean acetate concentration, center (random factor), age, weight loss, and fat-free mass (FFM). At baseline, no associations between plasma acetate and insulin sensitivity/resistance indices were found. We found a slight positive association between changes in acetate and changes in HOMA-IR (std 0.130, p = 0.033) in women, but not in men (std -0.072, p = 0.310) independently of age, weight loss and FFM. We were not able to confirm previously reported associations between acetate and insulin sensitivity in this large European cohort. The mechanisms behind the sex-specific relationship between LCD-induced changes in acetate and insulin sensitivity require further study.

Longer colonic transit time and hard stools are associated with increased gut microbiota diversity. Here, we investigate to what extent quantitative measures of (segmental) colonic transit time were related to gut microbiota composition, microbial metabolites, and gut-related parameters in a human cross-sectional study. Using radiopaque markers, (segmental) colonic transit time (CTT) was measured in 48 lean/overweight participants with long colonic transit but without constipation. Fecal microbiota composition was determined using 16S rRNA gene amplicon sequencing. Associations between gastrointestinal transit (segmental CTT and stool frequency and consistency), microbiota diversity and composition, microbial metabolites [short-chain fatty acids (SCFA), branched-chain fatty acids, and breath hydrogen], habitual diet, and gut-related host parameters [lipopolysaccharide-binding protein (LBP) and fecal calprotectin] were investigated using univariate and multivariate approaches. Long descending (i.e., distal) colonic transit was associated with increased microbial α-diversity but not with stool consistency. Using unweighted and weighted UniFrac distance, microbiota variation was not related to (segmental) CTT but to demographics, diet, plasma LBP, and fecal calprotectin. Bray–Curtis dissimilarity related only to stool consistency. Rectosigmoid and descending colonic transit were negatively associated with fecal SCFA and plasma acetate, respectively. This study suggests that the distal colon transit may affect not only microbiota diversity but also microbial metabolism. NEW & NOTEWORTHY We extend previous findings showing that long distal colonic transit time influences microbial diversification and fermentation, whereas stool consistency is related to microbiota composition in humans with a long colonic transit. This study puts the importance of the (distal) colonic site in microbiota ecology forward, which should be considered in future therapeutic studies targeting, for instance, short-chain fatty acid production to improve metabolic health.

The interplay of gut microbiota, host metabolism, and metabolic health has gained increased attention. Gut microbiota may play a regulatory role in gastrointestinal health, substrate metabolism, and peripheral tissues including adipose tissue, skeletal muscle, liver, and pancreas via its metabolites short-chain fatty acids (SCFA). Animal and human data demonstrated that, in particular, acetate beneficially affects host energy and substrate metabolism via secretion of the gut hormones like glucagon-like peptide-1 and peptide YY, which, thereby, affects appetite, via a reduction in whole-body lipolysis, systemic pro-inflammatory cytokine levels, and via an increase in energy expenditure and fat oxidation. Thus, potential therapies to increase gut microbial fermentation and acetate production have been under vigorous scientific scrutiny. In this review, the relevance of the colonically and systemically most abundant SCFA acetate and its effects on the previously mentioned tissues will be discussed in relation to body weight control and glucose homeostasis. We discuss in detail the differential effects of oral acetate administration (vinegar intake), colonic acetate infusions, acetogenic fiber, and acetogenic probiotic administrations as approaches to combat obesity and comorbidities. Notably, human data are scarce, which highlights the necessity for further human research to investigate acetate’s role in host physiology, metabolic, and cardiovascular health.

Aims/hypothesis: Gut microbial-derived short-chain fatty acids (SCFA) are believed to affect host metabolism and cardiometabolic risk factors. The present study aim was to investigate the effects of proximal and distal colonic infusions with the SCFA acetate on fat oxidation and other metabolic parameters in men. Methods: In this randomized, double-blind cross-over trial, six overweight/obese men (BMI 25-35 kg/m2) underwent two experimental periods: one with distal and one with proximal colonic sodium acetate infusions. A feeding catheter was endoscopically positioned at the beginning of each period and remained in the colon for three consecutive test days, enabling colonic acetate (100 mmol/L or 180 mmol/L) or placebo infusion during fasting conditions and after an oral glucose load (postprandial). Fat oxidation and energy expenditure were measured using an open-circuit ventilated hood system and blood samples were repeatedly collected for 2h during fasting and postprandial conditions. Results : Distal colonic 180 mmol/L acetate infusions increased fasting fat oxidation (1.78±0.28 vs -0.78±0.89 g fat 2h-1, P =0.015), fasting peptide YY (PYY, P =0.01) and postprandial glucose and insulin concentrations ( P

Evidence is accumulating that the gut microbiome is involved in the aetiology of obesity and obesity-related complications such as nonalcoholic fatty liver disease (NAFLD), insulin resistance and type 2 diabetes mellitus (T2DM). The gut microbiota is able to ferment indigestible carbohydrates (for example, dietary fibre), thereby yielding important metabolites such as short-chain fatty acids and succinate. Numerous animal studies and a handful of human studies suggest a beneficial role of these metabolites in the prevention and treatment of obesity and its comorbidities. Interestingly, the more distal colonic microbiota primarily ferments peptides and proteins, as availability of fermentable fibre, the major energy source for the microbiota, is limited here. This proteolytic fermentation yields mainly harmful products such as ammonia, phenols and branched-chain fatty acids, which might be detrimental for host gut and metabolic health. Therefore, a switch from proteolytic to saccharolytic fermentation could be of major interest for the prevention and/or treatment of metabolic diseases. This Review focuses on the role of products derived from microbial carbohydrate and protein fermentation in relation to obesity and obesity-associated insulin resistance, T2DM and NAFLD, and discusses the mechanisms involved.

The connection between the gut microbiota and the aetiology of obesity and cardiometabolic disorders is increasingly being recognized by clinicians. Our gut microbiota might affect the cardiometabolic phenotype by fermenting indigestible dietary components and thereby producing short-chain fatty acids (SCFA). These SCFA are not only of importance in gut health and as signalling molecules, but might also enter the systemic circulation and directly affect metabolism or the function of peripheral tissues. In this Review, we discuss the effects of three SCFA (acetate, propionate and butyrate) on energy homeostasis and metabolism, as well as how these SCFA can beneficially modulate adipose tissue, skeletal muscle and liver tissue function. As a result, these SCFA contribute to improved glucose homeostasis and insulin sensitivity. Furthermore, we also summarize the increasing evidence for a potential role of SCFA as metabolic targets to prevent and counteract obesity and its associated disorders in glucose metabolism and insulin resistance. However, most data are derived from animal and in vitro studies, and consequently the importance of SCFA and differential SCFA availability in human energy and substrate metabolism remains to be fully established. Well-controlled human intervention studies investigating the role of SCFA on cardiometabolic health are, therefore, eagerly awaited.

Purpose of review The purpose of this review was to highlight recent research developments on effects of the dietary fibre polydextrose (PDX) on appetite, satiety and energy intake and glucose metabolism. For this purpose, clinically relevant human studies were reviewed and putative mechanisms and pathways were discussed. Recent findings A number of acute human intervention studies provide strong indications for an energy and glucose metabolism-regulating role of PDX. These effects might be mediated via a reduced gastro-intestinal transit reducing glycaemia and insulinemia after PDX ingestion and the potential of PDX as soluble dietary fibre to alter the intestinal microbial composition, which might lead to changes in signalling in both peripheral and central pathways involved in energy metabolism and glucose homeostasis. Summary In acute studies, PDX seems to have an inhibiting effect on energy intake and satiety and to reduce glycaemic and insulinemic response through effect on gastro-intestinal transit time and macronutrient absorption as well as through effects of the microbial products such as short-chain fatty acids on energy and substrate metabolism. In particular, well controlled human intervention studies are required to confirm these effects in the long term. Overall, supplement PDX to the daily diet may be a promising approach for the management and treatment of obesity and associated metabolic disorders.

Background and aims: Gut derived short-chain fatty acids (SOFA), formed by microbial fermentation of dietary fibers, are believed to be involved in the etiology of obesity and diabetes. Previous data from our group showed that colonic infusions of physiologically relevant SOFA mixtures attenuated whole-body lipolysis in overweight men. To further study potential mechanisms involved in the antilipolytic properties of SOFA, we aimed to investigate the in vitro effects of SOFA incubations on intracellular lipolysis and signaling using a human white adipocyte model, the human multipotent adipose tissue-derived stem (hMADS) cells. Methods: hMADS adipocytes were incubated with mixtures of acetate, propionate, and butyrate or single SOFA (acetate, propionate and butyrate) in concentrations ranging between 1 mu mol/L and 1 mmol/L. Glycerol release and lipase activation was investigated during basal conditions and following p-adrenergic stimulation. Results: SOFA mixtures high in acetate and propionate decreased basal glycerol release, when compared to control (P < 0.05), while mixtures high in butyrate had no effect. Also, p-adrenergic receptor mediated glycerol release was not significantly altered following incubation with SOFA mixtures. Incubation with only acetate decreased basal (1 mu mol/L) and p-adrenergically (1 mmol/L and 1 mmol/L) mediated glycerol release when compared with control (P < 0.05). In contrast, butyrate (1 mu mol/L) slightly increased basal and p-adrenergically mediated glycerol release compared with control (P < 0.05), while propionate had no effect on lipolysis. The antilipolytic effect of acetate was accompanied by a reduced phosphorylation of hormone-sensitive lipase (HSL) at serine residue 650. In addition, inhibition of Gi G proteins following pertussis toxin treatment prevented the antilipolytic effect of acetate. Conclusion: The present data demonstrated that acetate was mainly responsible for the antilipolytic effects of SOFA and acts via attenuation of HSL phosphorylation in a Gi coupled manner in hMADS adipocytes. Therefore, the modulation of colonic and circulating acetate may be an important target to modulate human adipose tissue lipid metabolism.

The intestinal microbiota may contribute to the development of obesity by affecting host lipid metabolism and insulin sensitivity. To investigate the effects of microbiota manipulation on ex vivo basal and beta-adrenergically-stimulated lipolysis in human adipocytes, 36 obese men were randomized to amoxicillin (broad-spectrum antibiotic), vancomycin (narrow-spectrum antibiotic) or placebo treatment (7 d, 1500 mg/d). Before and after treatment, ex vivo adipose tissue lipolysis was assessed under basal conditions and during stimulation with the non-selective beta-agonist isoprenaline using freshly isolated mature adipocytes. Gene (targeted microarray) and protein expression were analyzed to investigate underlying pathways. Antibiotics treatment did not significantly affect basal and maximal isoprenaline-mediated glycerol release from adipocytes. Adipose tissue beta-adrenoceptor expression or post-receptor signalling was also not different between groups. In conclusion, 7 d oral antibiotics treatment has no effect on ex vivo lipolysis in mature adipocytes derived from adipose tissue of obese insulin resistant men.

© 2017 IEEE. Data quality control is one of the most time consuming activities within Research Infrastructures (RIs), especially when involving observational data and multiple data providers. In this work we report on our ongoing development of data rogues, a scalable approach to manage data quality issues for observational data within RIs. The motivation for this work started with the creation of the FLUXNET2015 dataset, which includes carbon, water, and energy fluxes plus micrometeorological and ancillary data measured in over 200 sites around the world. To create an uniform dataset, including derived data products, extensive work on data quality control was needed. The unpredictable nature of observational data quality issues makes the automation of data quality control inherently difficult. Developed based on this experience, the data rogues methodology allows for increased automation of quality control activities by systematically identifying, cataloging, and documenting implementations of solutions to data issues. We believe this methodology can be extended and applied to others domains and types of data, making the automation of data quality control a more tractable problem.

Short-chain fatty acids (SCFA), formed by microbial fermentation, are believed to be involved in the aetiology of obesity and diabetes. This study investigated the effects of colonic administration of physiologically relevant SCFA mixtures on human substrate and energy metabolism. In this randomized, double-blind, crossover study, twelve normoglycaemic men (BMI 25–35 kg/m2) underwent four investigational days, during which SCFA mixtures (200 mmol/L) high in either acetate (HA), propionate (HP), butyrate (HB) or placebo (PLA) were rectally administered during fasting and postprandial conditions (oral glucose load). Before and for two hours after colonic infusions, indirect calorimetry was performed and blood samples were collected. All three SCFA mixtures increased fasting fat oxidation (P P P

Author(s): Pastorello, GZ; Papale, D; Chu, H; Trotta, C; Agarwal, DA; Canfora, E; Baldocchi, DD; Torn, MS | Abstract: FLUXNET15, the latest update of the longest global record of ecosystem carbon, water, and energy fluxes, features improved data quality, new data products, and more open data sharing policies.

VAN DIJK, J.-W., R.J.F. MANDERS, E. E. CANFORA, W. VAN MECHELEN, F. HARTGENS, C. D. A. STEHOUWER, and L. J. C. VAN LOON. Exercise and 24-hGlycemic Control: Equal Effects for All Type 2 Diabetes Patients? Med. Sci. Sports Exerc., Vol. 45, No. 4, pp. 628-635, 2013. Purpose: We assessed the effect of a single bout of moderate-intensity exercise on subsequent 24-h glycemic control in 60 type 2 diabetes patients. Moreover, we examined whether individual responses to exercise were related to subjects' baseline characteristics, including age, body mass index, diabetes duration, exercise performance, medication, and HbA(1c) content. Methods: Sixty type 2 diabetes patients (insulin-treated, n = 23) participated in a randomized crossover experiment. Patients were studied on two occasions for 3 d under strict dietary standardization but otherwise free-living conditions. Parameters of glycemic control (means [95% confidence interval]) were assessed by continuous glucose monitoring over the 24-h period after a single bout of moderate-intensity endurance-type exercise or no exercise at all (control). Results: Type 2 diabetes patients experienced hyperglycemia (blood glucose >10 mmol.L-1) for as much as 8:16 h:min (6:44 to 9:48 h:min) per day. The prevalence of hyperglycemia was reduced by 31% to 5: 38 h: min (3: 17 to 7: 00 h: min) over the 24-h period after the exercise bout (P

Gut microbiota composition may play an important role in the development of obesity-related comorbidities. However, only few studies have investigated gender-differences in microbiota composition and gender-specific associations between microbiota or microbial products and insulin sensitivity. Insulin sensitivity (hyperinsulinemic-euglycemic clamp), body composition (dual energy X-ray absorptiometry), substrate oxidation (indirect calorimetry), systemic inflammatory markers and microbiota composition (PCR) were determined in male (n=15) and female (n=14) overweight and obese subjects. Bacteroidetes/Firmicutes-ratio was higher in men than in women (P=0.001). Bacteroidetes/Firmicutes-ratio was inversely related to peripheral insulin sensitivity only in men (men: P=0.003, women: P=0.882). This association between Bacteroidetes/Firmicutes-ratio and peripheral insulin sensitivity did not change after adjustment for dietary fibre and saturated fat intake, body composition, fat oxidation and markers of inflammation. Bacteroidetes/Firmicutes-ratio was not associated with hepatic insulin sensitivity. Men and women differ in microbiota composition and its impact on insulin sensitivity, implying that women might be less sensitive to gut microbiota-induced metabolic aberrations than men. This trial was registered at clinicaltrials.gov as NCT02381145.

BACKGROUND & AIMS: The gut microbiota affects host lipid and glucose metabolism, satiety, and chronic low-grade inflammation to contribute to obesity and type 2 diabetes. Fermentation end products, in particular the short-chain fatty acid (SCFA) acetate, are believed to be involved in these processes. We investigated the long-term effects of supplementation with galacto-oligosaccharides (GOS), an acetogenic fiber, on the composition of the human gut microbiota and human metabolism.METHODS: We performed a double-blinded, placebo-controlled, parallel intervention study of 44 overweight or obese (body mass index, 28-40 kg/m(2)) prediabetic men and women (ages, 45-70 y) from October 2014 through October 2015 in Maastricht, The Netherlands. The participants were assigned randomly to groups who ingested 15 g GOS or isocaloric placebo (maltodextrin) daily with their regular meals for 12 weeks. Before and after this period, we collected data on peripheral and adipose tissue insulin sensitivity, fecal microbiota composition, plasma and fecal SCFA, energy expenditure and substrate oxidation, body composition, and hormonal and inflammatory responses. The primary outcome was the effect of GOS on peripheral insulin sensitivity, measured by the hyperinsulinemic-euglycemic clamp method.RESULTS: Supplementation of diets with GOS, but not placebo, increased the abundance of Bifidobacterium species in feces by 5-fold (P = .009; q = 0.144). Microbial richness or diversity in fecal samples were not affected. We did not observe any differences in fecal or fasting plasma SCFA concentrations or in systemic concentrations of gut-derived hormones, incretins, lipopolysaccharide-binding protein, or other markers of inflammation. In addition, no significant alterations in peripheral and adipose tissue insulin sensitivity, body composition, and energy and substrate metabolism were found.CONCLUSIONS: Twelve-week supplementation of GOS selectively increased fecal Bifidobacterium species abundance, but this did not produce significant changes in insulin sensitivity or related substrate and energy metabolism in overweight or obese prediabetic men and women. ClincialTrials.gov number, NCT02271776.

Adiposity and the gut microbiota are both related to the risk of type 2 diabetes. We aimed to comprehensively examine how changes induced by a weight-loss diet intervention in gut microbiota-related metabolites, such as trimethylamineThis study included 510 overweight and obese individuals who were randomly assigned one of four diets varying in macronutrient intake. We examined associations of 6-month changes in blood metabolites (TMAO, choline, and l-carnitine) with improvements in body weight (BW), waist circumference (WC), body fat composition, fat distribution, and resting energy expenditure (REE).Individuals with a greater reduction of choline (Overweight and obese individuals who showed decreases in circulating choline or l-carnitine levels achieved greater improvements of adiposity and energy metabolism by eating a low-calorie weight-loss diet, suggesting that such metabolites are predictive of individuals' response to the treatment. Further investigations are necessary to confirm our findings, particularly in a population with prediabetes that is more representative of the U.S. population with obesity.

Gastrointestinal transit time may be an important determinant of glucose homeostasis and metabolic health through effects on nutrient absorption and microbial composition, among other mechanisms. Modulation of gastrointestinal transit may be one of the mechanisms underlying the beneficial health effects of dietary fibers. These effects include improved glucose homeostasis and a reduced risk of developing metabolic diseases such as obesity and type 2 diabetes mellitus. In this review, we first discuss the regulation of gastric emptying rate, small intestinal transit and colonic transit as well as their relation to glucose homeostasis and metabolic health. Subsequently, we briefly address the reported health effects of different dietary fibers and discuss to what extent the fiber-induced health benefits may be mediated through modulation of gastrointestinal transit.

Global obesity rates are increasing more and more. Short-chain fatty acids, the end products of fermentation of indigestible carbohydrates by intestinal bacteria, can influence metabolism and therefore play a role in the development of obesity and diabetes. The studies described in this dissertation show that the administration of short-chain fatty acids to the colon of overweight men increases energy expenditure and fat metabolism and reduces appetite and inflammation. The increase in the number of short-chain fatty acids in the colon by food intake can vitally contribute to the treatment or prevention of obesity and diabetes.

The book addresses in a comprehensive way the full greenhouse gases budget of the Italian landscape, focusing on land use and terrestrial ecosystems. In recent years there has been a growing interest in the role of terrestrial ecosystems with regard to the carbon cycle and only recently a regional approach has been considered for its specificity in terms of new methodologies for observations and models and its relevance for national policies on mitigation and adaptation to climate changes. In terms of methods this book describes the role of flux networks and data-driven models, airborne regional measurements of fluxes and specific sectoral approaches related to important components of the human and natural landscapes. There is also a growing need on the part of institutions, agencies and policy stakeholders for new data and analyses enabling them to improve their national inventories of greenhouse gases and their compliance with the UNFCCC process. In this respect the data presented is a basis for a full carbon accounting and available to relevant stakeholders for improvements and/or verification of national inventories. The wealth of research information is the result of a national project, CARBOITALY, which involved 15 Italian institutions and several researchers to provide new data and analyses in the framework of climate policies

Recent studies have highlighted the need to consider geological carbon sources when estimating the net ecosystem carbon balance (NECB) of terrestrial ecosystems located in areas potentially affected by geofluid circulation. We propose a new methodology using physical parameters of the atmospheric boundary layer to quantify the CO2 coming from deep ground origin in a steppe ecosystem located in the SE of Spain. Then, we compared published NECB estimates at the site with seasonal patterns of soil CO2 efflux and biological activity measured by satellite images over a 2-year period (2007/2008). The alpha grass ecosystem was a net carbon source (93.8 and 145.1 g C m−2 year−1, in 2007 and 2008, respectively), particularly as a result of large amounts of carbon released over the dry period that were not related to biological activity. While the highest ecosystem CO2 emission rates were measured over the dry period (reaching up to 15 μmol m−2 s−1), soil CO2 efflux rates (ca. 0.5 μmol m−2 s−1) and plant productivity were minimal during this period. After using a linear relationship between NECB and wind speed for different stability conditions and wind sectors, we estimated the geological flux FGEO (217.9 and 244.0 g C m−2 in 2007 and 2008, respectively) and subtracted it from the NECB to obtain the biological flux FBIO (−124.0 and −98.9 g C m−2 in 2007 and 2008, respectively). We then partitioned FBIO into gross primary productivity and ecosystem respiration and proved that, after removing FGEO, ecosystem respiration and soil CO2 efflux followed similar seasonal patterns. The annual contribution of the geological component to NECB was 49.6 and 46.7 % for the year 2007 and 2008, respectively. Therefore, it is clear that geological carbon sources should be quantified in those ecosystems located in areas with potential natural emission of geological gases to the surface.

Eddy covariance technique to measure CO2, water and energy fluxes between biosphere and atmosphere is widely spread and used in various regional networks. Currently more that 250 eddy covariance sites are active around the world measuring carbon exchange at high temporal resolution for different biomes and climatic conditions. These data are usually acquired using the same method but they need a set of corrections that are often differently applied to each site and in a subjective way. In this paper a new standardized set of corrections are proposed and the uncertainties introduced by these corrections are assessed for 8 different forest sites in Europe with a total of 12 yearly datasets. The uncertainties introduced on the two components GPP (Gross Primary Production) and TER (Terrestrial Ecosystem Respiration) are also discussed and a quantitative analysis presented . The results show that a standardized data processing is needed for an effective comparison across biomes and for underpinning inter-annual variability. The methodology presented in this paper has also been integrated in the European database of the eddy covariance measurements.

Eddy covariance technique to measure CO2, water and energy fluxes between biosphere and atmosphere is widely spread and used in various regional networks. Currently more than 250 eddy covariance sites are active around the world measuring carbon exchange at high temporal resolution for different biomes and climatic conditions. In this paper a new standardized set of corrections is introduced and the uncertainties associated with these corrections are assessed for eight different forest sites in Europe with a total of 12 yearly datasets. The uncertainties introduced on the two components GPP (Gross Primary Production) and TER (Terrestrial Ecosystem Respiration) are also discussed and a quantitative analysis presented. Through a factorial analysis we find that generally, uncertainties by different corrections are additive without interactions and that the heuristic u(*)-correction introduces the largest uncertainty. The results show that a standardized data processing is needed for an effective comparison across biomes and for underpinning interannual variability. The methodology presented in this paper has also been integrated in the European database of the eddy covariance measurements. Eddy covariance technique to measure CO2, water and energy fluxes between biosphere and atmosphere is widely spread and used in various regional networks. Currently more than 250 eddy covariance sites are active around the world measuring carbon exchange at high temporal resolution for different biomes and climatic conditions. In this paper a new standardized set of corrections is introduced and the uncertainties associated with these corrections are assessed for eight different forest sites in Europe with a total of 12 yearly datasets. The uncertainties introduced on the two components GPP (Gross Primary Production) and TER (Terrestrial Ecosystem Respiration) are also discussed and a quantitative analysis presented. Through a factorial analysis we find that generally, uncertainties by different corrections are additive without interactions and that the heuristic u(*)-correction introduces the largest uncertainty. The results show that a standardized data processing is needed for an effective comparison across biomes and for underpinning interannual variability. The methodology presented in this paper has also been integrated in the European database of the eddy covariance measurements. Eddy covariance technique to measure CO2, water and energy fluxes between biosphere and atmosphere is widely spread and used in various regional networks. Currently more than 250 eddy covariance sites are active around the world measuring carbon exchange at high temporal resolution for different biomes and climatic conditions. In this paper a new standardized set of corrections is introduced and the uncertainties associated with these corrections are assessed for eight different forest sites in Europe with a total of 12 yearly datasets. The uncertainties introduced on the two components GPP (Gross Primary Production) and TER (Terrestrial Ecosystem Respiration) are also discussed and a quantitative analysis presented. Through a factorial analysis we find that generally, uncertainties by different corrections are additive without interactions and that the heuristic u(*)-correction introduces the largest uncertainty. The results show that a standardized data processing is needed for an effective comparison across biomes and for underpinning interannual variability. The methodology presented in this paper has also been integrated in the European database of the eddy covariance measurements.